The primary aim of this work is the synthesis of a wide variety of water- soluble porphyrins and phthalocyanines bearing polyhedral carboranes and borane anion derivatives for potential use in boron neutron capture therapy. A secondary aim is the development of structure-activity relationships in this class of compounds to enable the rational design of new synthetic targets. The boranes to be attached include derivatives of the icosahedral carborane B10C2H12 and borane anion B12H122-, and the dodecahedral borane anion B10H102-. Both natural (dipropionic acid) and synthetic (tetraphenyl) porphyrins will serve as substrates for cage attachment, while in the phthalocyanines linkage will be effected through reactive side groups appended to the aromatic azaporphyrin rings. A variety of linkage chemistries are proposed which exploit the extensive derivative chemistries of boranes and nitrogen macrocyles. Water solubility in the carborane derivatives is to be achieved by several methods including carboxylation, cage opening, and sulfonylation of the synthetic macrocycles and by beta-pyrrole propionic acid residues in the natural porphyrin series. The charged borane anion derivatives are expected to be inherently water-soluble. Octanol/Water (buffer) partition coefficients at four near-physiologic pH's will be measured and used in conjunction with available computer modeling programs in an attempt to produce a database from which new potent, more tumor-selective compounds may be designed. In conjunction with the synthesis and design programs, a new rapid, cost-effective in vitro cell culture screening method will be used to provide information regarding tumor uptake. Previous work in our laboratory has demonstrated that: (1) water-soluble carboranyl porphyrins can be synthesized, often in excellent yield, (2) several such compounds give in vivo tumor boron concentrations and tumor/normal tissue ratios vastly exceeding that required for therapy, (3) one compound is efficacious in BNCT treatment of murine tumors, and (4) a range of optimal octanol/water partition coefficients for tumor uptake has been identified. In light of our very encouraging results, sustained funding is requested for future efforts.